This proposal examines the possible role of TRPV1, the capsaicin-noxious heat receptive ion channel, in modulating synaptic transmission between peripheral sensory neurons and dorsal horn spinal cord neurons. Although TRPV1 is normally not active at core body temperature, recent data in the literature have shown that either PLC activation or membrane depolarization can cause TRPV1 activation far below its nominal temperature threshold of activation of 43 degrees C. Electrophysiological studies performed at 37 degrees C in synaptic preparations will determine whether presynaptically-localized TRPV1 under conditions of either PLC activation or depolarization can modulate synaptic transmission in the spinal cord at physiological temperatures. As TRPV1 expressing sensory neurons are critical to the detection and processing of painful stimuli, the results of this project should have broad implications not only for the processing of normal painful stimuli but also towards understanding pathological pain states. Additionally, as TRPV1 has been reported to be expressed in both pyramidal neurons of the hippocampus and dopaminergic neurons of the substantia nigra, it is likely that the results of this study may have broad implications for synaptic physiology.